Project Summary Central venous stenosis (CVS) involves any one of the central veins such as subclavian, brachiocephalic and internal jugular veins, and superior vena cava in the patients with end stage renal disease. CVS is an important clinical problem as it currently affects 15-50% of ESRD patients and is thought to be responsible for 21-50% cases of vascular access malfunction. Both the diagnostic and the therapeutic landscapes of CVS represent areas of unmet need. Contrast venography is the standard-of-care for diagnosing CVS. However, this approach has several limitations including inaccurate determination of the extent of stenosis. In other clinical settings, the management of venous stenosis is increasingly influenced by the morphology of stenotic lesions. But venography fails to provide this information. While the endovascular interventions for CVS have encouraging short-term success rates, its long-term unassisted patency rates remain dismal. These interventions even increase the progression of the stenotic lesions in some cases. Currently, there are no methods for predicting which lesions are likely to improve or undergo accelerated progression from the intervention, and this represents a major knowledge gap in this area. An overarching objective of this project is to gain a deeper understanding of the types of lesions constituting CVS and their responses to the endovascular interventional therapies. This information will guide the development of a strategy to customize the intervention for those lesions that is likely to yield maximum therapeutic benefit. This pilot proposal represents an initial step towards this objective and explores the use of Intravascular ultrasound (IVUS) to overcome limitations of venography. IVUS uses radiofrequency ultrasound backscatter data to detect stenotic venous lesions. Image analysis will provide the morphological composition of the lesions. Aim 1 of this pilot study will compare venography to IVUS in detecting CVS to obtain a preliminary sensitivity of IVUS. Aim 2 will classify and map the morphology of stenotic lesions. The results from this pilot study will guide sufficiently powered future studies to demonstrate the superiority of IVUS compared to venography in diagnosing CVS. It will also seed interventional studies where the response to angioplasty will be compared based on the morphology of CVS lesions.